The focus of this SBIR Phase I project is to develop a microfluidic platform that serves as a surrogate microvasculature for studying factors influential in the onset of pulmonary hypertension. As envisioned, the resulting device platform will be capable of screening multi-parameter space for correlations between stresses due to fluid shear, viral infection and toxins and elucidated transforming growth factors. The proof-of- concept device will consist of a platform in which endothelial cells are cultured in situ and, after incubation, the chemical and physical properties of the surrounding fluid altered independently. The ability to create sensitively controlled chemical environments via microfluidics as well as subtle variations in stresses imparted to cells through fluid shear forces allows for control of multiple experimental parameters simultaneously. Variations imparted to channel geometry during fabrication will be designed to mimic bifurcation points in pulmonary arteries and fluid-control technology developed by Meta-Fluidics will allow full control of the conditions within the cell-containing capillaries. The specific aims of this project are to: 1) fabricate and demonstrate a multichannel microfluidic network conducive to microvascular endothelial cell adhesion and growth. 2) regulate the chemical and physical environments within cell-containing capillaries using Met fluidics flow control technology. 3) utilize the platform as a pulmonary mimic to investigate the effects of geometry and shear stress upon the transdifferentiation of healthy microvascular endothelial cells into plexiform lesions. Phase I success will set the stage for a larger Phase II effort focused on developing an to use "black box" that will coalesce geometric control, cell culturing and experimental control in a highly parallel fashion. The successful completion of this multi-phase SBIR project will immediately result in a technology that allows physical causes of pulmonary hypertension to be studied in a manner that has not been previously possible. More broadly, this technology will serve as a demonstration of the potential for microfluidics to produce systems that accurately mimic the morphology and function of endothelial-lined capillaries and will be applicable throughout diverse medical research disciplines.